Is NFIB p.Pro427Ser (c.1279C>T) pathogenic?

NFIB p.Pro427Ser (c.1279C>T) is classified Uncertain significance in NFIB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-09). Very rare (popmax 0.00275%, afr); Associated with Inborn genetic diseases.

What condition is associated with NFIB p.Pro427Ser (c.1279C>T)?

NFIB p.Pro427Ser (c.1279C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NFIB p.Pro427Ser (c.1279C>T) in the general population?

NFIB p.Pro427Ser (c.1279C>T) is very rare (popmax 0.00275%, afr) (gnomAD).

NFIB p.Pro427Ser

c.1279C>T · rs1358003647 · VCV3197517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00275%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.327	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00275% African / African-American · 2/72,616 alleles

Filtering AF 0.000457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000171%

Overall 0.00029% 4/1,381,676 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00275%	36,308
East Asian	0.00249%	40,218
European (non-Finnish)	8.78e-05%	1,138,666

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NFIB
Protein: p.Pro427Ser
Coding: c.1279C>T
MANE Select: NM_001190737
dbSNP: rs1358003647
Type: single nucleotide variant
Location: chr9:14116313 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.17 · 2 PDB

Full NFIB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NFIB p.Pro427Leu Uncertain significance ★ same residue
NFIB p.Asp309Val Uncertain significance ★★ ⚠ same condition
NFIB p.Glu305Gln Uncertain significance ★★ ⚠ same condition
NFIB p.Pro329Ser Uncertain significance ★★ ⚠ same condition
NFIB c.1061-1G>C Likely pathogenic ★ same condition
NFIB c.806+3A>C Uncertain significance ★ same condition
NFIB p.Arg81Cys Uncertain significance ★ ⚠ same condition
NFIB p.Asn219Asp Uncertain significance ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/nfib-p-pro427ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown